Inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn's disease, are characterized by abdominal pain, bloody diarrhea, and bowel-wall inflammation. Approximately 1 million Americans suffer from UC or Crohn's disease. In Western Europe and the United States the prevalence of UC is 70 to 150 per 100,000, while the prevalence of Crohn's disease is 4 to 100 per 100,000.
Although the cause of IBD is unknown, recent experimental and clinical studies suggest that initiation and pathogenesis of Crohn's disease and UC are multifactorial, involving interactions among genetic, environmental, and immune factors. Recently, IBD has been attributed to abnormal responses to environmental triggers in genetically susceptible individuals. Available data suggest that chronic gut inflammation may result from a dysfunctional immune response to components of normal gut flora. Although no specific bacteria have been implicated in the development of IBD in humans, in genetic models of IBD in mice and rats, specific bacteria have been shown to precipitate disease. In addition, environmental factors other than microbes play a role in the pathogenesis of IBD, as exemplified by the observation that smoking improves UC but worsens Crohn's disease.
There are no curative medical therapies for IBD, and even surgical bowel resection in Crohn's disease is not a definitive cure, since the majority of patients have recurrent disease. Current treatments for IBD fall into six classes: 1) corticosteroids, 2) aminosalicylates, 3) immunosuppressants, 4) antibiotics, 5) biologics, and 6) probiotics.
Aminosalicylate drugs, such as mesalamine (5-amino salicylic acid, or 5-ASA), are the mainstay of treatment for mild and moderate disease. These compounds are typically administered in the form of azo prodrugs, which are activated by colonic bacterial enzymes to release mesalamine as an anti-inflammatory agent. There are several commercially available drugs that contain mesalamine and that are used to treat inflammatory bowel conditions. The manufacturing processes of some of these drugs, however, suffer from inconsistencies, can be difficult to reproduce with the necessary degrees of accuracy and precision, or require specialized and expensive manufacturing equipment. Therefore, there exists a need for a solid dosage form of mesalamine with a high level of drug loading, a similar biological release profile to that of Pentasa®, and that can be manufactured with accuracy and precision.